Evidence map›Paper›PMID 41024254›Full record

ArticleBiology of sex differences2025

Multi-omics protein signaling networks identify sex-specific therapeutic candidates in lung adenocarcinoma.

Chen Chen, Enakshi Saha, Jonas Fischer, Marouen Ben Guebila, Viola Fanfani, Katherine H Shutta, Megha Padi, Kimberly Glass, Dawn L DeMeo, Camila M Lopes-Ramos and 1 more

Abstract read
In one paragraph

Article in Biology of sex differences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Chen ChenDepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.ORCID 0000-0002-8042-7201
Enakshi SahaDepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.ORCID 0000-0003-2938-539X
Jonas FischerDepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.
Marouen Ben GuebilaDepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.ORCID 0000-0001-5934-966X
Viola FanfaniDepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.ORCID 0000-0003-3852-6908
Katherine H ShuttaDepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.ORCID 0000-0003-0402-3771
Megha PadiDepartment of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, 85719, USA.ORCID 0000-0002-3446-4562
Kimberly GlassDepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.ORCID 0000-0003-4394-5779
Dawn L DeMeoChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.ORCID 0000-0001-9653-0636
Camila M Lopes-RamosDepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.ORCID 0000-0003-0284-7371
John QuackenbushDepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA. johnq@hsph.harvard.edu.ORCID 0000-0002-2702-5879

Funding

Respiratory Computational Discovery CoreP01HL114501 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHOI, MARY E · 2013 to 2025
$24.9M
Unraveling the Complexities of Risk and Mechanism in CancerR35CA220523 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI QUACKENBUSH, JOHN · 2018 to 2024
$6.0M
Leveraging Variant-perturbed Gene Regulation to Support Precision Medicine in COPDR01HL155749 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Kimberly Renee Glass · 2022 to 2026
$4.2M
Networks Tools to Understand Sex- and Gender-Specific Drivers of DiseaseR01HG011393 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI DEMEO, DAWN L, QUACKENBUSH, JOHN · 2021 to 2024
$2.1M
Unraveling the regulatory circuits that drive Merkel cell carcinomaR01CA251729 · NCI · UNIVERSITY OF ARIZONA · PI PADI, MEGHA · 2021 to 2025
$1.7M
Sex chromosome gene regulatory networks and COPDK01HL166376 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LOPES-RAMOS, CAMILA · 2023 to 2024
$324k
American Lung Association LCD-821824NCI NIH HHS R01 CA251729NCI NIH HHS R35 CA220523NHGRI NIH HHS R01 HG011393NHLBI NIH HHS K01 HL166376NHLBI NIH HHS P01 HL114501NHLBI NIH HHS R01 HL155749NIH HHS K01HL166376NIH HHS P01HL114501NIH HHS R01CA251729NIH HHS R01HL155749NIH HHS R35CA220523
6 · The paper itself

Abstract

backgroundLung adenocarcinoma shows distinct differences between males and females in incidence, prognosis, and treatment response, suggesting unique molecular mechanisms that remain underexplored. This study aims to identify sex-specific molecular signatures and therapeutic targets in lung adenocarcinoma using multi-omics approaches to inform personalized treatment strategies.

methodsWe conducted an integrative analysis of transcriptomic and proteomic data from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) datasets, comparing male and female lung adenocarcinoma profiles. Transcription factor activity was assessed using TIGER on gene expression data, while kinase activity was evaluated with PTM-SEA on proteomic data. These results were combined to build a kinase-transcription factor signaling network. Potential sex-specific drugs were identified using the PRISM drug screening database.

resultsThe analysis revealed significant sex-based differences in transcription factor and kinase activity. Notably, NR3C1, AR, and AURKA exhibited sex-biased expression and activity. The constructed signaling network highlighted druggable pathways linked to cancer-related processes, with distinct profiles in males and females. PRISM screening identified glucocorticoid receptor agonists and aurora kinase inhibitors as promising sex-specific therapeutic candidates.

conclusionsOur findings underscore the importance of considering sex differences in lung adenocarcinoma molecular profiles. The integration of transcriptomic and proteomic data reveals sex-specific pathways and potential therapies, paving the way for personalized treatment approaches tailored to male and female patients.

Indexed as

Adenocarcinoma of LungLung NeoplasmsSex CharacteristicsSignal TransductionFemaleHumansMaleMultiomicsProteomicsTranscriptomeAPOLLOCPTACDrug repurposingLung adenocarcinomaMulti-omicsPost-translational modificationsPRISMProtein signaling networkSex differencesTCGA

Identifiers

PMID41024254
PMCPMC12482505

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.